Stem cells are a population of cells capable of providing replacement cells for a given differentiated cell type (Blau et al. 2001). In the current proposal, stem cell-based technologies are applied to generate novel tissue-engineered, smart periodontal implants that use biomimetic strategies with the ultimate goal of achieving full regeneration of lost periodontal tissues. Mesenchymal periodontal tissues such as cementum, alveolar bone, and periodontal ligament are neural crest-derived entities that emerge from the dental follicle at the onset of root formation (Diekwisch 2001, 2002). In order to mimic the differentiation of periodontal cells from undifferentiated progenitors we are planning to recapitulate and/or mimic the molecular and cellular events that occur during periodontal tissue differentiation in the developing periodontium. Dental follicle and bone marrow mesenchymal stem cells have been isolated to determine the differentiation conditions necessary for these cells to mimic periodontal cells. In order to test the applicability of periodontal stem cells, we have established a series of model systems in which we will test the feasibility of using stern cells in conjunction with biomimetic scaffolds to generate bioengineered periodontal implants for improved periodontal regeneration. Hypothesis to be tested: Mesenchymal stem cells have the potential to generate and regenerate periodontal tissues, cementum, alveolar bone, and periodontal ligament. To test this hypothesis, we propose studies with the following Specific Aims: 1. To identify and isolate stem cells for periodontal tissue-engineering. 2. To establish and characterize stem cell lines for periodontal tissueengineering. 3. To test the conditions necessary to differentiate stem cells into periodontal cells in vitro. 4. To ask the question whether stem cells will mimic existing periodontal tissues following tissue implantation.